title: MicroRNAs of the miR-17∼92 family are critical regulators of T(FH) differentiation.
abstract: Follicular helper T cells (T(FH) cells) provide critical help to B cells during humoral immune responses. Here we report that mice with T cell-specific deletion of the miR-17∼92 family of microRNAs (miRNAs) had substantially compromised T(FH) differentiation, germinal-center formation and antibody responses and failed to control chronic viral infection. Conversely, mice with T cell-specific expression of a transgene encoding miR-17∼92 spontaneously accumulated T(FH) cells and developed a fatal immunopathology. Mechanistically, the miR-17∼92 family controlled the migration of CD4(+) T cells into B cell follicles by regulating signaling intensity from the inducible costimulator ICOS and kinase PI(3)K by suppressing expression of the phosphatase PHLPP2. Our findings demonstrate an essential role for the miR-17∼92 family in T(FH) differentiation and establish PHLPP2 as an important mediator of their function in this process.
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA.
authors.forename: Seung Goo
authors.initials: SG
authors.lastname: Kang
authors.forename: Wen-Hsien
authors.initials: WH
authors.lastname: Liu
authors.forename: Peiwen
authors.initials: P
authors.lastname: Lu
authors.forename: Hyun Yong
authors.initials: HY
authors.lastname: Jin
authors.forename: Hyung W
authors.initials: HW
authors.lastname: Lim
authors.forename: Jovan
authors.initials: J
authors.lastname: Shepherd
authors.forename: Daniel
authors.initials: D
authors.lastname: Fremgen
authors.forename: Eric
authors.initials: E
authors.lastname: Verdin
authors.forename: Michael B A
authors.initials: MB
authors.lastname: Oldstone
authors.forename: Hai
authors.initials: H
authors.lastname: Qi
authors.forename: John R
authors.initials: JR
authors.lastname: Teijaro
authors.forename: Changchun
authors.initials: C
authors.lastname: Xiao
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D005434:Flow Cytometry; D018858:Germinal Center / Q000166:cytology / Q000276:immunology*; D056724:Immunity, Humoral / Q000276:immunology; D007150:Immunohistochemistry; D060889:Inducible T-Cell Co-Stimulator Protein / Q000276:immunology; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000276:immunology*; D009687:Nuclear Proteins / Q000276:immunology*; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology; D010749:Phosphoprotein Phosphatases / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000201:enzymology / Q000276:immunology*
chemical_list: D060889:Inducible T-Cell Co-Stimulator Protein; D035683:MicroRNAs; D009687:Nuclear Proteins; D019869:Phosphatidylinositol 3-Kinases; D010749:Phosphoprotein Phosphatases; C556694:Icos protein, mouse; C575895:MIRN17-92 microRNA, mouse; C519282:PHLPP1 protein, mouse